APPLICATION OF BIOCATALYSTS FOR THE SUSTAINABLE POTENTIAL DRUGS

Abstract

Biocatalytically synthesis is an efficient synthesis of chiral building blocks of pharmaceutical, agrochemical and fine chemicals intermediates. This research work elicits mainly on exploring novel route of synthesis for the applications of biocatalyst using nitrilases, ketoreductases and transaminases. Ketoreducatses application for the chiral selective reduction of tert-butyl[5-(4-cyanobenzoyl)-2-fluorophenyl]carbamate to tert-butyl{5-[(4- cyanophenyl)(hydroxy)methyl]-2-fluorophenyl}carbamate. Commercially available enzymes were screened and the process optimised for commercial applications using ES-KRED-213 enzyme from syncozyme. The optimiation study includes co-solvent, pH, temperature for the reaction, substrate loading, enzyme loading and yield of the product. The purity of tert butyl{5-[(4-cyanophenyl) (hydroxy)methyl]-2-fluorophenyl}carbamate formed was >99% (RP-HPLC), and chiral purity >99% (NP-HPLC). The recovered product was confirmed and characterized with instrumental analysis using HPLC analysis, specific optical rotation, melting point and boiling point, LC-MS, ATR-FTIR, 1H NMR, and 13C NMR. Transaminase application for the chiral selective transamination of 1-(3- methylphenyl) ethan-1-one to (1R)-(3-methylphenyl)ethan-1-amine using ATA-025 from codexis. Commercially available enzymes screened and optimised the process for the commercial application. The variable such as co-solvent, enzyme loading, substrate loading, temperature, and pH for development of process displaying maximum conversion with good product formation and higher yield were optimized using one factor at a time approach and numerical optimization with Box Behnken Design, respectively. The purity of recovered product (1R)-(3-methylphenyl)ethan-1-amine formed was ≥99% (RP-HPLC), and chiral purity ≥98.5% (Chiral-GC), and it was also confirmed and characterized with instrumental methods using melting point, LC-MS, ATR-FTIR, and 1H NMR